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Metformin is widely used to treat hyperglycemia in individuals with type 2 diabetes. Recently the LKB1/AMP-activated protein kinase (LKB1/AMPK) pathway was proposed to mediate the action of metformin on hepatic gluconeogenesis. However, the molecular mechanism by which this pathway operates had remained elusive. Surprisingly, here we have found that in mice(More)
Unlike the adjustable gastric banding procedure (AGB), Roux-en-Y gastric bypass surgery (RYGBP) in humans has an intriguing effect: a rapid and substantial control of type 2 diabetes mellitus (T2DM). We performed gastric lap-band (GLB) and entero-gastro anastomosis (EGA) procedures in C57Bl6 mice that were fed a high-fat diet. The EGA procedure specifically(More)
BACKGROUND & AIMS Glucose-6 phosphatase (Glc6Pase) is the last enzyme of gluconeogenesis and glycogenolysis, previously assumed to be expressed in the liver and kidney only, conferring on both tissues the capacity to produce endogenous glucose in blood. METHODS Using Northern blotting and reverse-transcription polymerase chain reaction and a highly(More)
At variance with the current view that only liver and kidney are gluconeogenic organs, because both are the only tissues to express glucose-6-phosphatase (Glc6Pase), we have recently demonstrated that the Glc6Pase gene is expressed in the small intestine in rats and humans and that it is induced in insulinopenic states such as fasting and diabetes. We used(More)
Soluble dietary fibers promote metabolic benefits on body weight and glucose control, but underlying mechanisms are poorly understood. Recent evidence indicates that intestinal gluconeogenesis (IGN) has beneficial effects on glucose and energy homeostasis. Here, we show that the short-chain fatty acids (SCFAs) propionate and butyrate, which are generated by(More)
PEPCK is a key enzyme of gluconeogenesis in liver and kidney. Recently, we have shown that small intestine also contributes to the endogenous glucose production in insulinopenia in rats and that glutamine is the main precursor of glucose synthesized in this tissue. The expression of the PEPCK gene in rat and human small intestine and the effect of(More)
Insulin initiates diverse hepatic metabolic responses, including gluconeogenic suppression and induction of glycogen synthesis and lipogenesis. The liver possesses a rich sinusoidal capillary network with a higher degree of hypoxia and lower gluconeogenesis in the perivenous zone as compared to the rest of the organ. Here, we show that diverse vascular(More)
Using Northern blot with a specific glucose-6-phosphatase (Glc6Pase) cDNA probe and enzymatic activity determination, we studied the effect of streptozotocin-induced diabetes on Glc6Pase in rat gluconeogenic tissues. The Glc6Pase mRNA abundance was increased four to five times in both the liver and kidney of diabetic rats. This was correlated with a(More)
We have studied the time course of hepatic and renal microsomal glucose-6 phosphatase (Glc-6Pase) during long-term fasting in the rat. Liver microsomal Glc-6Pase increases up to 48 hr and significantly decreases after 48 hr of fasting. The following activities were determined at 0, 24, 48, 72 and 96 hr: 0.31 +/- 0.02; 0.50 +/- 0.02; 0.54 +/- 0.03; 0.44 +/-(More)
We have recently shown that the Ca.EGTA and Mg.EDTA complexes, but not free Ca2+ or Mg2+, inhibit the liver glucose-6-phosphatase (Mithieux, G., Vega, F. V., Beylot, M., and Riou, J. P. (1990) J. Biol. Chem. 265, 7257-7259). In this work, we report that, when complexed with Mg2+, two endogenous dicarboxylic keto acids (alpha-ketoglutarate (alpha-KG) and(More)